Chronic Intermittent Hypobaric Hypoxia Ameliorates Renal Vascular Hypertension Through Up-regulating NOS in Nucleus Tractus Solitarii

Neurosci Bull. 2019 Feb;35(1):79-90. doi: 10.1007/s12264-018-00330-z. Epub 2019 Jan 7.

Abstract

Chronic intermittent hypobaric hypoxia (CIHH) is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension (RVH). In this study, RVH was induced by the 2-kidney-1-clip method (2K1C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii (NTS) in anesthetized rats. Evoked excitatory postsynaptic currents (eEPSCs) and spontaneous EPSCs (sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase (nNOS) and endothelial NOS (eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHH-treated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and eNOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via up-regulating NOS expression in the NTS.

Keywords: Chronic intermittent hypobaric hypoxia; Excitatory postsynaptic current; Nitric oxide; Renal sympathetic nerve activity; Renal vascular hypertension.

MeSH terms

  • Animals
  • Baroreflex / physiology
  • Blood Pressure / drug effects
  • Hypertension / metabolism*
  • Hypoxia / chemically induced*
  • Kidney / drug effects
  • Kidney / metabolism
  • Male
  • Nitric Oxide Synthase Type I / drug effects
  • Nitric Oxide Synthase Type I / metabolism*
  • Rats, Sprague-Dawley
  • Solitary Nucleus / metabolism*

Substances

  • Nitric Oxide Synthase Type I